We are investigating the development of serum sickness in humans with the use of various in-depth clinical and immunological analyses. Thirty-five (35) patients with various hematological dyscrasias treated with horse anti-thymocyte globulin (ATG) infused over a 10 or 28 day course have been evaluated. The majority of patients had aplastic anemia (29/35). Thirty (30/35) patients developed clinical signs and symptoms of serum sickness 8-14 days after the start of ATG infusion that consisted of fever/malaise (94%), rashes (80%), arthralgias (66%), gastrointestinal complaints (57%), cephalgias (49%), myalgias (31%), blurred vision (31%), and lymphadenopathy (14%). We have also discovered a peculiar cutaneous marker occurring on the hands and feet that is specific for serum sickness. The formation of immune complexes and the consumption of complement paralleled the development of the serum sickness symptoms. Immunoglobulin levels increased several-fold in patients developing serum sickness with the most dramatic increases in the immunoglobulin associated with allergic diseases, IgE. Abnormalities in renal and liver function were noted during serum sickness. Acute phase reactants as measured by erythrocyte sedimentation rates, titers of C-reactive proteins, fibronectin and beta-2 microglobulin became markedly elevated during the course of infusion of ATG. Hematopoietic recovery occurred in all patients that did not develop serum sickness as compared to a 50% recovery rate in those that did develop serum sickness.